J Korean Diabetes Assoc.  2002 Apr;26(2):91-99.

Effect of Advanced Glycation End Products on Rat Aortic Vascular Smooth Muscle Cells

• Song JY
• Ihm SH
• Suh JY
• Cho YJ
• Yoo HJ
• Park SW
• Ihm JH

Abstract

BACKGROUND: Diabetes mellitus is an epidemiologically proven risk factor for atherosclerosis. Advanced glycation end products (AGE) have been implicated in the pathogenesis of many diabetic vascular complications. AGE not only change the physicochemical properties of proteins, but also induce a wide range of cell-mediated responses. However, biological effects of AGE on the vascular smooth muscle cells (VSMCs) have not been fully explained despite of presence of an AGE-receptor on the VSMCs.
METHODS
In order to test whether AGE promotes atherosclerosis by stimulation of the growth promoting signal transduction pathways in the VSMCs, the proliferation of rat aortic VSMCs cultured in the presence of AGE-BSA with/without anti-AGE antibodies, the MAP kinase inhibitor and antioxidants was measured. The VSMCs (1 x 104 cells in 24-well plates) isolated from the aorta of Sprague-Dawley rats were incubated for 48 hours and the proliferation was assessed by a MTT assay.
RESULTS
AGE-BSA increased the proliferation of rat aortic VSMCs by 1.5~1.6 fold at the g/mL level. The stimulatory effect of AGE-BSA (5 microgram/mL) was blocked by the anti-AGE antibodies (100 microgram/mL). PD98059 at 50 M inhibited the AGE - BSA - induced VSMC proliferation, suggesting that MAP kinase activation might be responsible for the proliferative response of the VSMCs to AGE. AGE - BSA - induced VSMC proliferation was also attenuated by N-acetylcysteine (1 micro M) and butylated hydroxyanisole (10 micro M), implying that increased intracellular oxidative stress might be also involved in the proliferative response to AGE.
CONCLUSION
These results suggest AGE play a role in diabetic atherosclerosis by stimulating of the growth promoting signal transduction pathways in the VSMCs.

Keyword

Advanced glycation end products; Vascular smooth muscle cells

MeSH Terms

Acetylcysteine
Animals
Antibodies
Antioxidants
Aorta
Atherosclerosis
Butylated Hydroxyanisole
Diabetes Mellitus
Diabetic Angiopathies
Glycosylation End Products, Advanced*
Muscle, Smooth, Vascular*
Oxidative Stress
Phosphotransferases
Rats*
Rats, Sprague-Dawley
Risk Factors
Signal Transduction
Acetylcysteine
Antibodies
Antioxidants
Butylated Hydroxyanisole
Glycosylation End Products, Advanced
Phosphotransferases